This application addresses Broad Challenge Area 4 (Clinical Research) and Specific Challenge Topic 04- MH-105 (Developing interventions and service delivery models for the transition to adulthood). The goal of our research is to conduct a four-site (UCLA, Emory, North Carolina, Yale) pilot randomized trial (N = 96), to determine the efficacy of a 6-month Family-Focused Treatment (FFT) in comparison with Treatment-As-Usual (TAU) in enhancing functional outcomes, stabilizing symptoms, and preventing or delaying the onset of full psychosis in youth aged 12-25 years who meet criteria for a prodromal risk syndrome according to the Structured Interview for Prodromal Syndromes (SIPS). Our primary, secondary, and tertiary hypotheses, respectively, are that at-risk probands will respond better to FFT than TAU at 6- and 12-month follow-ups, in terms of (1) school and social functioning, family functioning, and parental distress, (2) symptom trajectories (SIPS scores), and (3) time to first onset of full psychosis. Subjects will be drawn from the participants in a currently funded prospective, longitudinal study elucidating predictors and mechanisms of conversion to psychosis (North American Prodrome Longitudinal Study, or NAPLS), on which the four sites collaborate. Subjects will be interviewed every 6 months for 2 years to assess positive and negative symptoms, academic and social functioning, family functioning, and conversion to psychosis. A major advantage of our proposal is that the costs of recruitment and clinical evaluation will be borne by the NAPLS grant, which allows the resources of the Challenge Grant to be concentrated on performing the proposed Treatment Study. Recent progress in risk ascertainment methodology has enabled reliable identification of persons with prodromal or "clinical high-risk" syndromes, 35% of whom develop psychosis within 2 and 1/2 years. This paradigm provides an opportunity for developing and testing interventions in the prodromal phase, before the onset of full psychosis and accumulation of substantial functional disability. Psychosocial interventions appear to be well suited to address issues of motivational deficits and functional disability in the psychosis prodrome. Given our present state of knowledge regarding the mechanisms of psychosis onset, and given that initial studies of antipsychotic drugs in prodromal patients have produced discouraging results in terms of prevention, a reduction in functional disability may represent a more achievable target in the short term than a reduction in psychosis incidence. We have developed and piloted a version of FFT for prodromal youth (FFT-PY) consisting of psychoeducation, communication training, and problem-solving skills training. In randomized trials, adults and adolescents with bipolar disorder and children at-risk for bipolar disorder undergoing FFT improved symptomatically and functionally compared to patients in brief psychoeducational control conditions. Further, an open trial of family psychoeducation for youth at risk for psychosis demonstrated symptomatic and functional improvements relative to baseline scores. However, no randomized controlled study has examined the efficacy of FFT for reducing functional disability and preventing functional deterioration or onset of full psychosis. In view of the improvements in quality of life and the reductions in costs of care that have occurred with preventive approaches to cardiovascular disease, diabetes, and certain forms of cancer, the field of psychiatry is in need of a major commitment to an early detection/prevention framework for its most debilitating syndromes - the psychotic disorders. The prodromal risk syndrome criteria have resulted in clinical algorithms that are highly effective in predicting onset of full psychosis. However, such knowledge will be of limited utility if we lack the means of intervening in the pre-onset phase in a way that either reduces the likelihood of progression to full psychosis, the accumulation of functional disability, or both. There are currently no cost- effective, evidence-based psychosocial approaches to psychosis prevention. Preventing the neurotoxic effects of early episodes, before these illnesses become chronic, and minimizing the psychosocial sequelae of early episodes, may do much to prevent the long-term disability caused by psychosis and thereby have a major impact on public health. Our study will take the critical next step by performing an initial efficacy test of a highly promising family-focused intervention designed to stabilize symptoms and improve social and role functioning in at risk youth. PUBLIC HEALTH RELEVANCE: Preventing psychotic disorders such as schizophrenia and associated functional disability could relieve an enormous burden of personal and family suffering and economic losses to society. This 4-site project aims to conduct a pilot randomized trial to determine the efficacy of a family-focused treatment in comparison with treatment-as-usual in enhancing functional outcomes, stabilizing symptoms, and preventing or delaying the onset of full psychosis in transitional age youth with prodromal symptoms. The results of this study will be crucial for the development of cost-effective, evidence-based psychosocial approaches to psychosis prevention and thus will have major implications for public health.